3M syndrome 2

Summary

3M syndrome 2 (MONDO:0013039) is a disease caused by OBSL1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: OBSL1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 291

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	3M syndrome 2
Mondo ID	MONDO:0013039
MeSH	C567862
OMIM	612921
UMLS	C2752041
MedGen	414168
GARD	0015591
Is cancer (heuristic)	no

Also known as: 3-M syndrome 2 · 3-M syndrome caused by mutation in OBSL1 · 3M syndrome 2 · 3M2 · OBSL1 3-M syndrome · three M syndrome 2 · three M syndrome type 2

Data availability: 291 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › 3-M syndrome › 3M syndrome 2

Related subtypes (2): 3M syndrome 1, 3M syndrome 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

291 retrieved; paginated sample, class counts are floors:

110 uncertain significance, 64 conflicting classifications of pathogenicity, 44 benign, 30 likely pathogenic, 18 benign/likely benign, 17 pathogenic, 5 likely benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
916539	NM_015311.3(OBSL1):c.[1273dup];[35dup]		Pathogenic	criteria provided, single submitter
998035	NM_015311.3(OBSL1):c.[1273dup;836G>A]		Pathogenic	no assertion criteria provided
1046	NM_015311.3(OBSL1):c.1149C>A (p.Cys383Ter)	OBSL1	Pathogenic	criteria provided, single submitter
1047	NM_015311.3(OBSL1):c.1256_1265del (p.Arg419fs)	OBSL1	Pathogenic	no assertion criteria provided
1049	NM_015311.3(OBSL1):c.1465C>T (p.Arg489Ter)	OBSL1	Pathogenic	no assertion criteria provided
1236172	NM_015311.3(OBSL1):c.2164del (p.Asp722fs)	OBSL1	Pathogenic	criteria provided, multiple submitters, no conflicts
1333217	NM_015311.3(OBSL1):c.458dup (p.Leu154fs)	OBSL1	Pathogenic	criteria provided, multiple submitters, no conflicts
1687280	NM_015311.3(OBSL1):c.1068_1075dup (p.Val359fs)	OBSL1	Pathogenic	criteria provided, single submitter
1705252	NM_015311.3(OBSL1):c.427dup (p.Ala143fs)	OBSL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
195306	NM_015311.3(OBSL1):c.1273dup (p.Thr425fs)	OBSL1	Pathogenic	criteria provided, multiple submitters, no conflicts
2572584	NM_015311.3(OBSL1):c.1260dup (p.Val421fs)	OBSL1	Pathogenic	criteria provided, multiple submitters, no conflicts
2690347	NM_015311.3(OBSL1):c.1359dup (p.Glu454fs)	OBSL1	Pathogenic	criteria provided, single submitter
3585688	NM_015311.3(OBSL1):c.2249dup (p.Tyr750Ter)	OBSL1	Pathogenic	criteria provided, single submitter
374349	NM_015311.3(OBSL1):c.2474del (p.Val825fs)	OBSL1	Pathogenic	no assertion criteria provided
3896354	NM_015311.3(OBSL1):c.103del (p.Val35fs)	OBSL1	Pathogenic	criteria provided, single submitter
429882	NM_015311.3(OBSL1):c.2032C>T (p.Gln678Ter)	OBSL1	Pathogenic	criteria provided, multiple submitters, no conflicts
599223	NM_015311.3(OBSL1):c.1125dup (p.Glu376Ter)	OBSL1	Pathogenic/Likely pathogenic	no assertion criteria provided
617511	NM_015311.3(OBSL1):c.457_458delinsT (p.Gly153fs)	OBSL1	Pathogenic	no assertion criteria provided
870250	NM_015311.3(OBSL1):c.848del (p.Gly283fs)	OBSL1	Pathogenic	criteria provided, single submitter
976857	NM_015311.3(OBSL1):c.35dup (p.Cys13fs)	OBSL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324825	NM_015311.3(OBSL1):c.4085del (p.Leu1362fs)	OBSL1	Likely pathogenic	criteria provided, single submitter
1486927	NM_015311.3(OBSL1):c.1535-3_1535-2del	OBSL1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705464	NM_015311.3(OBSL1):c.2292_2320dup (p.Ile774delinsArgArgTrpMetGlyAlaAsnThrValTer)	OBSL1	Likely pathogenic	criteria provided, single submitter
1723324	NM_015311.3(OBSL1):c.921delinsCC (p.Tyr308fs)	OBSL1	Likely pathogenic	criteria provided, single submitter
2498079	NM_015311.3(OBSL1):c.5556_5557insTC (p.Lys1853fs)	OBSL1	Likely pathogenic	criteria provided, single submitter
2692499	NM_015311.3(OBSL1):c.2222C>G (p.Ser741Ter)	OBSL1	Likely pathogenic	criteria provided, single submitter
3257733	NM_015311.3(OBSL1):c.1838-2_1838-1del	OBSL1	Likely pathogenic	criteria provided, single submitter
3341398	NM_015311.3(OBSL1):c.3682C>T (p.Arg1228Ter)	OBSL1	Likely pathogenic	criteria provided, single submitter
3374954	NM_015311.3(OBSL1):c.2134+2T>C	OBSL1	Likely pathogenic	criteria provided, single submitter
3382459	NM_015311.3(OBSL1):c.3080dup (p.Glu1028fs)	OBSL1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
OBSL1	Definitive	Autosomal recessive	3M syndrome 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OBSL1	Orphanet:2616	3M syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
OBSL1	HGNC:29092	ENSG00000124006	O75147	Obscurin-like protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OBSL1	Obscurin-like protein 1	Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OBSL1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OBSL1	287	ubiquitous	marker	right testis, left testis, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OBSL1	4,202

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OBSL1	O75147	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Neddylation	1	47.4×	0.021	OBSL1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cardiac myofibril assembly	1	1296.3×	0.003	OBSL1
positive regulation of dendrite morphogenesis	1	887.0×	0.003	OBSL1
protein localization to Golgi apparatus	1	802.5×	0.003	OBSL1
regulation of mitotic nuclear division	1	624.1×	0.003	OBSL1
Golgi organization	1	133.8×	0.008	OBSL1
cytoskeleton organization	1	132.7×	0.008	OBSL1
microtubule cytoskeleton organization	1	121.2×	0.008	OBSL1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
OBSL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	OBSL1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
OBSL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.